Impact of renal impairment on pharmacokinetics, safety, and tolerability of funobactam, combined with imipenem and cilastatin.

In 30 seconds

This phase 1, open-label study assessed the pharmacokinetics and safety of a single intravenous dose of funobactam with imipenem and cilastatin in participants across five renal-function categories, including end-stage renal disease requiring hemodialysis. Drug exposure increased as renal impairment worsened; in the hemodialysis cohort, AUC0-∞ geometric mean ratios versus normal renal function were 9.58 for funobactam, 2.69 for imipenem, and 15.15 for cilastatin. Treatment was well tolerated, with no deaths, severe adverse events, or adverse-event-related discontinuations.

Key findings

• In participants with end-stage renal disease requiring hemodialysis, AUC0-∞ ratios versus normal renal function were 9.58 [7.59, 12.10] for funobactam, 2.69 [2.06, 3.52] for imipenem, and 15.15 [10.8, 21.3] for cilastatin.
• Plasma clearance of all three drugs correlated with creatinine clearance and estimated glomerular filtration rate (r ≥0.93).
• No deaths, severe adverse events, or discontinuations due to adverse events occurred.

Why it matters

Renal function was strongly associated with exposure to the three-drug regimen, particularly for funobactam and cilastatin in end-stage renal disease. These pharmacokinetic findings help characterize how impaired clearance may affect drug exposure and provide a basis for considering dosing in renal impairment, while the single-dose safety findings offer limited information about tolerability.

What to keep in mind

The study evaluated a single dose in an open-label phase 1 design; it does not establish safety or efficacy with repeated treatment.